Mutations in the X-linked (period) per gene disrupt circadian rhythms of pupal eclosion and adult locomoter activity in D. melanogaster (Konopka and Benzer, 1971) by shortening (per allele) or lengthening (per1) allele) the period of the rhythm or abolishing the rhythm altogether (per(o)allele). Expression of the per gene is essential for circadian regulation of these behaviors. However, the biological activity of per protein is unknown. Analysis of a recently identified arrhythmic mutation, timeless (tim) (Sehgal et al., 1994), suggests that nuclear localization of per protein may be an important part of the regulatory mechanism (Vosshall et al., 1994). The goal of this proposal is to understand how per functions by structure/function analysis in vivo of regions of per protein that are highly conserved among different species of Drosophila and Antheraea pernyi. In some cases, these are predicted to have secondary structural motifs that are known to mediate protein- protein interactions. In addition, the domain of per that interacts with tim will be mapped, in an effort to elucidate the nature of per's interaction with tim.